A Clinical Study to Investigate the Efficacy and Safety of an Investigational Combination Therapy With BNT324 and BNT327 in Patients With Advanced Lung Cancer
Purpose
This study aims to investigate the combination of BNT324, a B7-H3 antibody-drug conjugate (ADC) with BNT327, a programmed death-ligand 1 (PD-L1) and vascular endothelial growth factor (VEGF) bispecific antibody, in participants with advanced/metastatic or relapsed/progressive small cell lung cancer (SCLC) and non small cell lung cancer (NSCLC).
Condition
- Advanced Lung Cancer
Eligibility
- Eligible Ages
- Over 18 Years
- Eligible Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- Aged ≥18 years at the time of giving informed consent. - Histological or cytological confirmed unresectable advanced/metastatic lung cancer. Histological classification may be based on tumor samples prior to metastatic disease. Participants with mixed histology must be classified based on the main component. Participants with NSCLC are eligible with any or no PD-L1 expression. Participants with AGA-positive disease must have received targeted therapy prior to enrollment in this study. - Part 1: Participants with NSCLC and SCLC - Part 2 Cohort 1: Participants with NSCLC (subpopulation 1) AGA negative, 1L - Part 2 Cohort 2: Participants with SCLC, 2L+ - Part 2 Cohort 3: Participants with NSCLC (subpopulation 1) AGA negative, 2L+ - Part 2 Cohort 4: Participants with NSCLC (subpopulation 2) AGA negative, 1L - Part 2 Cohort 5: Participants with NSCLC (subpopulation 2) AGA negative, 2L+ - Part 2 Cohort 6: Participants with NSCLC AGA positive - Part 2 Cohort 7: Participants with SCLC, 1L - Have measurable disease defined by RECIST version 1.1. - Have an Eastern Cooperative Oncology Group performance status of 0 or 1. - Have a life expectancy of ≥12 weeks.
Exclusion Criteria
- Prior treatment with B7-H3 targeted therapy. - Prior treatment with ADC with topoisomerase inhibitor (e.g., datopotamab deruxtecan, trastuzumab deruxtecan). Note: This exclusion applies to participants in the first-line/treatment-naïve cohorts in the advanced/metastatic setting. Prior treatment with ADC with topoisomerase inhibitor payload is only allowed for participants in the second-line plus cohorts in the advanced/metastatic setting. - Is a candidate to locoregional treatment (including surgical resection, stereotactic radiotherapy or tumor ablation) with potential to induce complete or near complete response and prolonged tumor control (sometimes described as "radical" intent), per investigator's assessment. - Has a history of significant hematologic toxicity to prior lines of therapy, as assessed by investigator, e.g., Grade 4 febrile neutropenia or recurrent/persistent Grade 3 to 4 neutropenia. NOTE: Other protocol defined Inclusion/Exclusion criteria may apply to all or some participants depending on the cohort.
Study Design
- Phase
- Phase 1/Phase 2
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel Assignment
- Primary Purpose
- Treatment
- Masking
- None (Open Label)
Arm Groups
| Arm | Description | Assigned Intervention |
|---|---|---|
|
Experimental Part 1 - BNT324 + BNT327 combination therapy |
Escalating combination dose levels of BNT324 and BNT327 to define RP2D and RP2D-1 for NSCLC and SCLC. |
|
|
Experimental Part 2 - Cohort 1: RP2D of BNT324 + BNT327 and RP2D-1 of BNT324 + BNT327 |
In subpopulation 1 of NSCLC actionable oncogenic alteration (AGA) negative, first-line (1L) |
|
|
Experimental Part 2 - Cohort 2: RP2D of BNT324 + BNT327 and RP2D-1 of BNT324 + BNT327 |
In SCLC, second-line plus (2L+) |
|
|
Experimental Part 2 - Cohort 3: RP2D of BNT324 + BNT327 |
In subpopulation 1 of NSCLC AGA negative, 2L+ |
|
|
Experimental Part 2 - Cohort 4: RP2D of BNT324 + BNT327 |
In subpopulation 2 of NSCLC AGA negative, 1L |
|
|
Experimental Part 2 - Cohort 5: RP2D of BNT324 + BNT327 |
In subpopulation 2 of NSCLC AGA negative, 2L+ |
|
|
Experimental Part 2 - Cohort 6: RP2D of BNT324 + BNT327 |
In NSCLC AGA positive |
|
|
Experimental Part 2 - Cohort 7: RP2D of BNT324 + BNT327 |
In SCLC, 1L |
|
Recruiting Locations
Beverly Hills 5328041, California 5332921 90212
Los Angeles 5368361, California 5332921 90048
Santa Monica 5393212, California 5332921 90404
Iowa City 4862034, Iowa 4862182 52242
Hackensack 5098706, New Jersey 5101760 07601
New York 5128581, New York 5128638 10021
New York 5128581, New York 5128638 10029
Cleveland 5150529, Ohio 5165418 44195
Dallas 4684888, Texas 4736286 75246
Houston 4699066, Texas 4736286 77030
Tyler 4738214, Texas 4736286 75702
Fairfax 4758023, Virginia 6254928 22031
More Details
- Status
- Recruiting
- Sponsor
- BioNTech SE
Detailed Description
This is a two-part study designed to evaluate and establish two safe combination dose levels (recommended Phase 2 dose [RP2D] and a lower/another combination dose level [RP2D-1]) of BNT324 with BNT327 (Part 1), to determine the optimal combination dose (dose optimization [DO]) in NSCLC and SCLC lead indication cohorts at the RP2D and RP2D-1, to evaluate the preliminary efficacy in selected lung cancer cohorts at the highest combination dose level (in a signal seeking Part 2), and to confirm the clinical efficacy of BNT324 in combination with BNT327 at the optimal dose level in participants with advanced lung cancer in expansion cohorts (proof-of-concept [POC] cohorts). The study consists of a screening period, a treatment period, a safety follow-up period, and a long-term survival follow-up period. In Part 1 participants with histologically or cytologically confirmed relapsed or progressive lung cancer (both SCLC and NSCLC are eligible) will receive BNT324 in combination with BNT327 using a dose escalation design. In Part 2 of the study, BNT324 will be studied in combination with BNT327 at the RP2D compared to RP2D-1 in participants with advanced metastatic treatment-naïve NSCLC (DO Cohort 1) and relapsed/progressive SCLC after failure of cytotoxic chemotherapy with or without immuno-oncology (IO) (DO Cohort 2). The totality of the available data (e.g., safety, efficacy, pharmacokinetics etc.) will be reviewed to select the optimal dose. After the optimal dose is selected, additional participants in each cohort may be enrolled in the selected optimal dose. In the signal seeking cohorts (Cohort 3-7), participants will receive BNT324 in combination with BNT327 at the RP2D from Part 1. A predefined number of participants in Part 2 Cohort 1 and Cohort 2 will be randomized to one of the two dose levels (RP2D and RP2D-1) selected from Part 1 in a 1:1 ratio. Additional participants in Part 2 Cohort 1 and Cohort 2 may be enrolled in the selected optimal dose to further assess the efficacy and safety profile. No randomization is planned for any other cohort in Part 2 or Part 1.